Tipping the Balance of Autism Risk: Potential Mechanisms Linking Pesticides and Autism Janie F. Shelton, Irva Hertz-Picciotto, and Isaac N. Pessah Autism spectrum disorders (ASDs) have been increasing in many parts of the world and a portion of cases are attributable to environmental exposures with mounting evidence suggesting gestational pesticides exposures as strong candidates to cause autism. Because multiple developmental processes are implicated in ASDs during gestation and early life, biological plausibility is more likely if these agents can be shown to affect core pathophysiological features. In California, a 600% increased incidence in autism was observed among children up to 5 years of age for births from 1990 to 2001, yet only one-third of the rise could be explained by identified factors such as changing diagnostic criteria and a younger age at diagnosis (Hertz-Picciotto and Delwiche 2009). Pesticide exposure as a cause of autism – research now shows gestational pesticides exposures are strong candidates to cause autism http://ehp.niehs.nih.gov/1104553/

Across the United States, autism spectrum disorders (ASD) are now estimated to affect 1 in 88 eight-year-olds, with much higher prevalence in boys (1 in 54) than girls (1 in 252) (Centers for Disease Control and Prevention 2012). Autism is a heterogeneous, behaviorally defined condition often diagnosed in children prior to age 3 years. Although each individual diagnosis must meet specific criteria related to deficits in social interaction and language and to the presence of repetitive behaviors or restricted interests, autism phenotypes vary widely, even among concordant twins (Le Couteur et al. 1996). Adequate levels of in utero thyroid hormones are critical for brain development. Maternal thyroid impairment has been suggested as an underlying mechanism for developmental impairments resulting from exposures to environmental chemicals such as PCBs and polybrominated diphenyl ethers (PBDEs) used as flame retardants (Winneke 2011). Pesticides have been found to interfere with thyroid function by preventing iodine uptake [e.g., mancozeb, thiocyanates, 2,4-D (2,4-dichlorophenoxyacetic acid)] and peroxidation (e.g., aminotriazole, endosulfan, malathion), and by preventing the conversion of thyroxine (T4) to triiodothyronine (T3) (e.g., aminotriazole, dimethoate, fenvalerate) (Colborn 2004). In a review of the effects of mild-to-moderate iodine deficiency in humans, diminished maternal T4 was associated with disorders of mental and/or psychomotor development (Zimmermann 2007). Pesticides are composed of a parent product, inert ingredients, and in some cases agonists that enhance the functionality of the parent compound, and all of these ingredients may be degraded to metabolites that also distribute throughout the body. Consequently, pesticide formulations represent a mixture of compounds that might contribute to observed effects. Difficulties in distinguishing the effects of metabolites versus parent compounds may have confounded associations observed in many studies of urinary metabolites and neurodevelopment, and very few studies have examined the main effects or effect modification of exposure to piperonyl butoxide, which slows the metabolism of several types of pesticides by inhibiting cytochrome P450 enzymes. Although pesticides are a biologically plausible contributor to autism, research in several critical areas is needed to understand cognitive and behavioral consequences of gestational exposure in humans. First, animal studies suggest critical windows of exposure, yet in humans the window or windows of biologic susceptibility remain unknown, and would be expected to vary by mechanism. Second, studies of nontoxic, environmentally relevant doses are needed to understand the effects of developmental neurotoxicity in the context of a background of genetic susceptibilities. Third, the vast majority of exposures occur in combination with exposures to other ubiquitous and/or persistent compounds such as flame retardants, plasticizers, and other pesticides. More research on combinations of exposures may reveal interactions between environmental exposures, such as effect modification by chemical additives to pesticide compounds. In light of the recently revised prevalence estimates of autism (1 in 88), large birth cohorts, such as the National Children’s Study (NCS), which aim to enroll women at pregnancy and follow the children over time, are well positioned to obtain enough cases and to examine prenatal exposures prospectively. Pending accurate and reliable exposure estimates in critical time windows, and enrollment of approximately 100,000 children resulting in 1,000 or more cases of autism, NCS can contribute greatly to our understanding of these associations. Finally, more case–control studies with large populations of participants with confirmed diagnoses of autism that examine environmental exposures in relation to severity of the core domains of language impairment, social avoidance, and repetitive behaviors or insistence on sameness may shed light on possible exposure-related endophenotypes. Although we have described several possible avenues by which pesticide exposure may influence autism, the dearth of studies on large occupational and pregnancy cohorts with adequate exposure assessment impedes our understanding of a) whether pesticides are consistently associated with autism risk, and b) if so, which pesticide compounds and which components of those compounds might actually contribute to autism risk. Grandjean and Landrigan (2006) hypothesized that our exposure to chemicals that have not been adequately tested for developmental neurotoxicity has led to a silent pandemic. Further research is warranted to provide the evidence base that can ultimately lead to reducing or eliminating these potentially damaging exposures through changes to regulatory policy, consumer behavior, or dietary choices. For the complete article click the link here